A Multicentre Randomized, Double-blind, Placebo Controlled, Dose-finding, Phase 2 Study (MARS-17) of GSK3858279 in Adult Participants With Moderate to Severe Pain Due to Knee Osteoarthritis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 314
- 试验地点
- 1
- 主要终点
- Change From Baseline in Weekly Average of Average Daily Knee Pain Intensity Using Numeric Rating Scale at Week 12
研究概览
简要总结
This is dose-finding study of GSK3858279 in participants with moderate to severe knee osteoarthritis pain. The purpose of this study is to investigate and provide the data necessary to select the optimal effective and safe dose(s) of GSK3858279.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant must be 40 to 80 years of age inclusive
- •OA of the index knee as defined by symptomatic for ≥ 6 months with a clinical diagnosis of OA as per American College of Rheumatology (ACR) clinical diagnosis criteria.
- •Kellgren and Lawrence (KL) score ≥ 2 on X-ray in the index knee
- •An average of the average daily pain score of ≥4 and less than or equal to (≤) 9 by the 11-point NRS (0-10)
- •Body mass index (BMI) of < 40 kilogram per meter square (kg/m^2) (inclusive).
- •Capable of giving signed informed consent.
排除标准
- •History or presence of cardiovascular, renal, gastrointestinal, lymphatic disorders which in the opinion of the investigator would interfere with the study procedures and/or assessments.
- •History or current evidence of any inflammatory arthritis such as rheumatoid arthritis, infective arthritis, Paget's disease, osteonecrosis, osteoporotic fracture, or any other joint disease that in the Investigator's opinion would interfere with the assessment of pain and other symptoms of osteoarthritis.
- •History of significant trauma or surgery to a knee or hip within the last 6 months.
- •Current immunodeficiency diseases including but not limited to acquired immunodeficiency disorder or immunoglobulin deficiency.
- •Current or previous active Mycobacterium tuberculosis
- •History or evidence of clinically significant multiple or severe drug allergies
- •History of malignancy within the last 5 years, except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
- •Alanine transaminase (ALT) >1.5 times upper limit of normal (ULN).
- •Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35 percent (%)
- •Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
- •Evidence of renal insufficiency, indicated by estimated creatinine clearance < 60 milliliter/ minute (mL/min)/1.73 square meter (m^2) at screening.
- •Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
研究组 & 干预措施
GSK3858279 - 60 mg weekly
Participants received GSK3858279 60 milligram (mg) SC injection once per week for 16 weeks.
干预措施: GSK3858279 (Drug)
GSK3858279 - 240 mg every 2 weeks
Participants received GSK3858279 240 mg SC injection every other week for 16 weeks. Placebo was given in the intervening week to maintain the blinding.
干预措施: GSK3858279 (Drug)
GSK3858279 - 240 mg weekly
Participants received GSK3858279 240 mg SC injection once per week for 16 weeks.
干预措施: GSK3858279 (Drug)
GSK3858279 - 360 mg weekly
Participants received GSK3858279 360 mg SC injection once per week for 16 weeks.
干预措施: GSK3858279 (Drug)
Placebo
Participants received placebo subcutaneous (SC) injection once per week for 16 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Weekly Average of Average Daily Knee Pain Intensity Using Numeric Rating Scale at Week 12
时间窗: Baseline (Day -7 to Day -1) and at Week 12
Change from Baseline in knee pain due to Osteoarthritis were reported by weekly average of average daily pain numeric rating scale (NRS) at Week 12. The pain NRS is an 11-point scale (ranging from 0-10) for self-reporting of average daily knee pain where 0 indicates no pain, and 10 indicates the worst possible pain. For each participant, the weekly average of average daily pain score was calculated using the mean value of available daily pain scores falling in the assessment window for each week. A negative change from baseline indicates an improvement in pain. Participants were asked to complete the pain NRS questionnaire at the same time in the evening each day. Baseline scores were assigned based on an average of 7 days prior to day 1 dosing visit. Posterior mean change from baseline, 95 percent (%) credible interval (CI) was derived using Bayesian mixed model repeated measures. The data presented are the posterior mean with 95% confidence interval refers to 95% credible interval.
次要结局
- Time to Maximum Plasma Concentration (Tmax) of GSK3858279(Pre-dose: Day 1, Weeks 1, 2, 4, 8, 10, 11 and 12)
- Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score At Week 12(Baseline (Day 1) and at Week 12)
- Change From Baseline in WOMAC Physical Function Subscale Score at Week 12(Baseline (Day 1) and at Week 12)
- Change From Baseline in Patient Global Assessment Of Disease (PtGA) at Week 12(Baseline (Day 1) and at Week 12)
- Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs of Special Interest (AESI)(Up to 31 weeks)
- Number of Participants With Greater Than or Equal to (>=) Grade 3 Hematological/Clinical Chemistry Abnormalities According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCICTCAE)(Up to 31 weeks)
- Maximum Concentration (Cmax) of GSK3858279(Pre-dose: Day 1, Weeks 1, 2, 4, 8, 10, 11 and 12)
- Pre-Dose (Trough) Concentration at the End of the Dosing Interval (Ctau) of GSK3858279(Pre-dose: Day 1, Weeks 1, 2, 4, 8, 10, 11 and 12)
- Average Concentration Over a Dosing Interval (Cavg) of GSK3858279(Pre-dose: Day 1, Weeks 1, 2, 4, 8, 10, 11 and 12)
- Area Under the Time-Concentration Curve (AUC) Over the Dosing Interval (0-Tau) (AUC[0-Tau]) of GSK3858279(Pre-dose: Day 1, Weeks 1, 2, 4, 8, 10, 11 and 12)